Competitive binding of UBPY and ubiquitin to the STAM2 SH3 domain revealed by NMR

FEBS Lett. 2012 Sep 21;586(19):3379-84. doi: 10.1016/j.febslet.2012.07.047. Epub 2012 Jul 25.

Abstract

To date, the signal transducing adaptor molecule 2 (STAM2) was shown to harbour two ubiquitin binding domains (UBDs) known as the VHS and UIM domains, while the SH3 domain of STAM2 was reported to interact with deubiquitinating enzymes (DUBs) like UBPY and AMSH. In the present study, NMR evidences the interaction of the STAM2 SH3 domain with ubiquitin, demonstrating that SH3 constitutes the third UBD of STAM2. Furthermore, we show that a UBPY-derived peptide can outcompete ubiquitin for SH3 binding and vice versa. These results suggest that the SH3 domain of STAM2 plays versatile roles in the context of ubiquitin mediated receptor sorting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry*
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Binding, Competitive
  • Endopeptidases / chemistry
  • Endopeptidases / metabolism*
  • Endosomal Sorting Complexes Required for Transport / chemistry*
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Interaction Domains and Motifs
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Ubiquitin / chemistry
  • Ubiquitin / metabolism*
  • Ubiquitin Thiolesterase / chemistry
  • Ubiquitin Thiolesterase / metabolism*
  • src Homology Domains

Substances

  • Adaptor Proteins, Signal Transducing
  • Endosomal Sorting Complexes Required for Transport
  • Recombinant Proteins
  • STAM2 protein, human
  • Ubiquitin
  • Endopeptidases
  • USP8 protein, human
  • Ubiquitin Thiolesterase